Asymmctric Orgnocatalytic Michael Addition Reaction Of α,β-Unsaturalted Aldehydes

Michael addition reaction is an important nucleophilic reaction.α,β-Unsaturated aldehyde is a valuable Michael acceptor, which reacts with various electron donors to affordβ-functionalization aldehyde derivatives. These derivatives are key chiral intermediates, building blocks or biologic active substances.In the first part, we studied the asymmetric organocatalytic Michael addition reactions of Ni (Ⅱ) complexes of glycine Schiff base toα,β-unsaturated aldehydes. After condition screening, the optimal reaction condition was obtained and applied to different enals. The reaction was carried out efficiently in the mixed solvent of MeOH and CH2Cl2 using 10 mol% of J(?)rgensen-Hayashi catalyst and 20 mol% of PhCOOLi, followed by reduction using NaBH4. The desired products were produced in up to 98% yield and 49:1 dr value. The enantioselectivity was up to 99% and all the ee values were>90%. The product was further treated to give a six-member lactone heterocycle with two adjacent chiral centers. This study offered an alternative approach to chiralα-amino acid derivatives and six-member heterocycles.Next, the asymmetric vinylogous Michael reactions ofα,β-unsaturated aldehydes withγ-butenolide was explored, which served as a powerful tool for the synthetically chiralγ-butenolide skeleton. The reaction of 2(5H)-furan to differentα,β-unsaturated aldehydes were proceeded successfully in MeOH by 10 mol% of J(?)rgensen-Hayashi catalyst and 20 mol% of LiOAc, in up to 94% yield and 2.8:1 dr value. The enantioselectivity was excellent (up to 99%), and all the ee values were>94%.Finally, the enantioselective organocatalytic phospha-Michael reaction ofα,β-unsaturated aldehydes with diaryl phosphine oxides was investigated, which provides a new and easy method to construct chiral P-C bond and chiral phosphine oxide derivitives with excellent chemo- and enantioselectivity. The reaction of diaryl phosphine oxides and differentα,β-unsaturated aldehydes was firstly conducted efficiently catalyzed by 20 mol% of J(?)rgensen-Hayashi catalyst at -20℃in CH2Cl2 with excellent enantioselectivity. Most of the ee values were>90%. The desired products were produced in up to 98% yield.